Complement deficiency promotes cutaneous wound healing in mice

Stavros Rafail, Ioannis Kourtzelis, Periklis G Foukas, Maciej M Markiewski, Robert A DeAngelis, Mara Guariento, Daniel Ricklin, Elizabeth A Grice, John D Lambris

Research output: Contribution to journalArticlepeer-review


Wound healing is a complex homeostatic response to injury that engages numerous cellular activities, processes, and cell-to-cell interactions. The complement system, an intricate network of proteins with important roles in immune surveillance and homeostasis, has been implicated in many physiological processes; however, its role in wound healing remains largely unexplored. In this study, we employ a murine model of excisional cutaneous wound healing and show that C3(-/-) mice exhibit accelerated early stages of wound healing. Reconstitution of C3(-/-) mice with serum from C3(+/+) mice or purified human C3 abrogated the accelerated wound-healing phenotype. Wound histology of C3(-/-) mice revealed a reduction in inflammatory infiltrate compared with C3(+/+) mice. C3 deficiency also resulted in increased accumulation of mast cells and advanced angiogenesis. We further show that mice deficient in the downstream complement effector C5 exhibit a similar wound-healing phenotype, which is recapitulated in C5aR1(-/-) mice, but not C3aR(-/-) or C5aR2(-/-) mice. Taken together, these data suggest that C5a signaling through C5aR may in part play a pivotal role in recruitment and activation of inflammatory cells to the wound environment, which in turn could delay the early stages of cutaneous wound healing. These findings also suggest a previously underappreciated role for complement in wound healing, and may have therapeutic implications for conditions of delayed wound healing.

Original languageEnglish
Pages (from-to)1285-91
Number of pages7
JournalJournal of Immunology
Issue number3
Publication statusPublished - 1 Feb 2015

Bibliographical note

Copyright © 2015 by The American Association of Immunologists, Inc.


  • Animals
  • Complement C3/deficiency
  • Complement C5a/genetics
  • Complement System Proteins/deficiency
  • Disease Models, Animal
  • Humans
  • Inflammation/genetics
  • Male
  • Mice
  • Mice, Knockout
  • Models, Immunological
  • Neovascularization, Physiologic/genetics
  • Receptors, Complement/genetics
  • Skin/immunology
  • Wound Healing/genetics

Cite this